High rates of congenital malformations that have been observed in areas of Azerbaijan where there is extensive environmental contamination from heavy metals, pesticides and oily wastes that are also present at lower levels in Texas and other parts of the United States. Risks for congenital malformations among births in an area with high levels of contamination such as Azerbaijan will be useful in estimating potential birth defects risk in and around Superfund sites in the US. Collaborative research with Azeri physicians and scientists will carry out a concurrent/prospective case-control study based on cases identified from multiple sources. Exposure to environmental contaminants will be determined through a combination of environmental assessment and maternal questionnaires. Genetic variations in 4 loci as they relate to risk for environmentally induced human congenital malformations will also be investigated. Specifically, we will assess potential associations between genetic variation on the following genes, RFC1, MTHFD, NAT2 and CYP1A1, and potential developmental toxicants associated with maternal occupational and ambient exposures and the risk of neural tube defects (NTDs), orofacial clefts (CLP), and other midline defects. Based upon preliminary data obtained during a recent to Azerbaijan, we can anticipate identifying approximately 50 cases with CLP, 30 NTD cases, and a comparable number of other midline defect cases per year. The proposed case-control studies will identify cases from a retrospective five-year period (1996-2000) and for three years (2001-2003) prospectively. Results from epidemiologic, environmental and genetic studies will provide data to show possible causal linkages between Superfund contaminants and human disease.